The extensively branched vascular network within the placenta is vital for materno-fetal exchange, and inadequate development of this network is implicated in the pregnancy disorder fetal growth restriction (FGR), where babies are born pathologically small. Placental mesenchymal stem/stromal cells (pMSCs) and placental macrophages both reside in close proximity to blood vessels within the placenta, where they are thought to promote angiogenesis via paracrine mechanisms. However, the relationship between pMSCs, macrophages and placental vascular development has not yet been examined. We aimed to determine if inadequate paracrine stimulation of placental vascular development by pMSCs and macrophages during pregnancy may contribute to the inadequate vascularisation seen in FGR. Media conditioned by MSCs from FGR placentae significantly inhibited endothelial tube formation, compared to conditioned media derived from normal pMSCs. Similarly, macrophages exposed to media conditioned by FGR pMSCs were less able to stimulate endothelial tube formation in comparison to macrophages exposed to media conditioned by normal pMSCs. While MSCs from normal placentae produce a combination of angiogenic and anti-angiogenic cytokines, there were no significant differences in the secretion of the anti-angiogenic cytokines thrombospondin-1, insulin growth factor binding protein-4, or decorin between normal and FGR pMSCs that could explain how FGR pMSCs inhibited endothelial tube formation. Together, these data suggest a dysregulation in the secretion of paracrine factors by pMSCs in FGR placentae. These findings illustrate how cross talk between pro-angiogenic cell types in the placenta may be crucial for adequate angiogenesis.

中文翻译：

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生长受限的胎盘的间充质干/基质细胞是血管生成的不良刺激物。

胎盘内广泛分支的血管网络对于母胎交换至关重要，该网络的发育不充分与妊娠期胎儿生长受限（FGR）有关，胎儿在病理上出生时很小。胎盘间充质干/基质细胞（pMSC）和胎盘巨噬细胞均位于胎盘内的血管附近，据认为它们通过旁分泌机制促进血管生成。然而，尚未研究pMSC，巨噬细胞和胎盘血管发育之间的关系。我们旨在确定怀孕期间pMSC和巨噬细胞对旁分泌对胎盘血管发育的刺激是否不足，可能导致FGR中血管生成不足。与源自正常pMSC的条件培养基相比，以FGR胎盘的MSC为条件的培养基显着抑制了内皮管的形成。类似地，与暴露于由正常pMSCs调节的培养基的巨噬细胞相比，暴露于FGR pMSCs调节的培养基的巨噬细胞刺激内皮管形成的能力较差。虽然正常胎盘的MSC产生血管生成和抗血管生成细胞因子的组合，但正常和FGR pMSCs的抗血管生成细胞因子thrombospondin-1，胰岛素生长因子结合蛋白4或decorin的分泌没有显着差异。可以解释FGR pMSCs如何抑制内皮管的形成。总之，这些数据表明FGR胎盘中pMSC分泌旁分泌因子失调。